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Human Skin Microbiome Engineering

Project description

Human skin as a disease-sensing biological device

The skin microbiome can be used to incorporate novel functionalities in the host. This is because it is easily accessible and in direct contact with the host, has low immunogenicity and can be genetically manipulated. With this in mind, the EU-funded HuSME project aims to engineer the human skin commensal Cutibacterium acnes (C. acnes) as a disease-sensing biological device that will detect atopic dermatitis and produce an anti-inflammatory molecule in response. To achieve this, it will develop a vector and a methodology for efficient gene delivery into C. acnes. It will also construct synthetic gene circuits that will allow C. acnes to detect inflammatory markers in vitro and consequently secrete anti-inflammatory signals. The project will help to advance human microbiome genetic engineering.

Objective

The skin microbiome constitutes an attractive platform to incorporate novel functionalities to the host, due to accessible location, tight contact with the host, low immunogenicity, and easier genetic manipulation, among other reasons. I will adopt a translational synthetic biology approach to engineer the human skin commensal C. acnes (formerly P. acnes) as a disease-sensing biological device (“biodevice”) with therapeutic activity. Precisely, engineered C. acnes will detect atopic dermatitis (AD, the most common chronic inflammatory disease worldwide) and respond by producing an anti-inflammatory molecule. First, I will develop a vector and a methodology for efficient gene delivery into C. acnes. Next, I will construct synthetic gene circuits that will allow C. acnes to detect inflammatory markers in vitro and to respond by secreting anti-inflammatory signals. Finally, I will use the C. acnes biodevice as an in vivo therapeutic product: I will apply the engineered bacteria on a mouse model of AD and evaluate its potential as a therapeutic tool capable of disease-sensing and regulated maintenance of skin homeostasis. This project will contribute to the emerging field of human microbiome genetic engineering, will inspire and guide future efforts towards microbiome repurposing for therapeutics, and has the potential to provide exploitable results and better therapeutic options for AD patients.

Coordinator

UNIVERSIDAD POMPEU FABRA
Net EU contribution
€ 160 932,48
Address
PLACA DE LA MERCE, 10-12
08002 Barcelona
Spain

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Region
Este Cataluña Barcelona
Activity type
Higher or Secondary Education Establishments
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Total cost
€ 160 932,48